DK3022210T3 - NEW AZABENZIMIDAZOLD DERIVATIVES. - Google Patents

Info

Publication number

DK3022210T3

DK3022210T3 DK14738531.4T DK14738531T DK3022210T3 DK 3022210 T3 DK3022210 T3 DK 3022210T3 DK 14738531 T DK14738531 T DK 14738531T DK 3022210 T3 DK3022210 T3 DK 3022210T3

Authority

DK

Denmark

Prior art keywords

group

alkyl

chloro

pyridin

imidazo

Prior art date

2013-07-17

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 description 350
• 150000001875 compounds Chemical class 0.000 description 295
• 238000001819 mass spectrum Methods 0.000 description 192
• 239000000543 intermediate Substances 0.000 description 148
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
• 239000000203 mixture Substances 0.000 description 108
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
• 108010011376 AMP-Activated Protein Kinases Proteins 0.000 description 72
• 102000014156 AMP-Activated Protein Kinases Human genes 0.000 description 72
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• 229940093499 ethyl acetate Drugs 0.000 description 42
• 235000019439 ethyl acetate Nutrition 0.000 description 42
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• 238000011282 treatment Methods 0.000 description 35
• 150000003839 salts Chemical class 0.000 description 34
• 201000010099 disease Diseases 0.000 description 29
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 26
• 239000012267 brine Substances 0.000 description 25
• 206010012601 diabetes mellitus Diseases 0.000 description 25
• DTGSFFWQUULHIF-UHFFFAOYSA-N imino-dimethyl-oxo-$l^{6}-sulfane Chemical compound CS(C)(=N)=O DTGSFFWQUULHIF-UHFFFAOYSA-N 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• -1 C5-7-cycloalkenyl Chemical group 0.000 description 24
• 238000006243 chemical reaction Methods 0.000 description 24
• 239000003814 drug Substances 0.000 description 24
• YWRNLGJAKHHQHK-OQUNMALSSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CC1(C)OB(OC1(C)C)c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl YWRNLGJAKHHQHK-OQUNMALSSA-N 0.000 description 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• 229940124597 therapeutic agent Drugs 0.000 description 19
• 239000000460 chlorine Substances 0.000 description 18
• 229910052801 chlorine Inorganic materials 0.000 description 18
• 125000000623 heterocyclic group Chemical group 0.000 description 18
• 239000008194 pharmaceutical composition Substances 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 239000000243 solution Substances 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 14
• NOIDOGJGONCMSZ-UGESXGAOSA-N (3R,3aR,6R,6aR)-6-[5-(4-bromophenyl)-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(Br)cc1 NOIDOGJGONCMSZ-UGESXGAOSA-N 0.000 description 13
• 241000282414 Homo sapiens Species 0.000 description 13
• 208000008589 Obesity Diseases 0.000 description 13
• 229910052786 argon Inorganic materials 0.000 description 13
• 229910052794 bromium Inorganic materials 0.000 description 13
• 239000000872 buffer Substances 0.000 description 13
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 13
• 230000001404 mediated effect Effects 0.000 description 13
• 235000020824 obesity Nutrition 0.000 description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 13
• 230000004913 activation Effects 0.000 description 12
• 125000003118 aryl group Chemical group 0.000 description 12
• 229910052731 fluorine Inorganic materials 0.000 description 12
• 125000001072 heteroaryl group Chemical group 0.000 description 12
• 229910052763 palladium Inorganic materials 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 11
• 239000003112 inhibitor Substances 0.000 description 11
• 229910052740 iodine Inorganic materials 0.000 description 11
• 125000005555 sulfoximide group Chemical group 0.000 description 11
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000012300 argon atmosphere Substances 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• 239000000284 extract Substances 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 125000004076 pyridyl group Chemical group 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 10
• WBMREWGOOFBREU-CDRKEARJSA-N (3R,3aR,6R,6aR)-6-[5-[4-(4-bromophenyl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(Br)cc1 WBMREWGOOFBREU-CDRKEARJSA-N 0.000 description 9
• NZCOCDVQDMXXNP-UGESXGAOSA-N 4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]benzoic acid Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)C(O)=O NZCOCDVQDMXXNP-UGESXGAOSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• 208000030159 metabolic disease Diseases 0.000 description 9
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 206010020772 Hypertension Diseases 0.000 description 8
• 239000000556 agonist Substances 0.000 description 8
• 125000004429 atom Chemical group 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 230000003647 oxidation Effects 0.000 description 8
• 238000007254 oxidation reaction Methods 0.000 description 8
• 125000004193 piperazinyl group Chemical group 0.000 description 8
• 125000003386 piperidinyl group Chemical group 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 8
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 7
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
• MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical group CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 239000008103 glucose Substances 0.000 description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• JNNUCBXQAMEEBI-KBUPBQIOSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-iodo-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(I)nc12 JNNUCBXQAMEEBI-KBUPBQIOSA-N 0.000 description 6
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 6
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• 102000004877 Insulin Human genes 0.000 description 6
• 108090001061 Insulin Proteins 0.000 description 6
• 206010022489 Insulin Resistance Diseases 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6
• 239000005557 antagonist Substances 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
• 239000000969 carrier Substances 0.000 description 6
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• 229940125396 insulin Drugs 0.000 description 6
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 6
• 235000015320 potassium carbonate Nutrition 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 125000005551 pyridylene group Chemical group 0.000 description 6
• 150000003254 radicals Chemical class 0.000 description 6
• 239000012453 solvate Substances 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• VZPGBGXVBHZSQG-RSZYDNOISA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-(N,S-dimethylsulfonimidoyl)pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound ClC=1C=C2C(=NC1C1=CC=C(C=C1)C1=NC=C(C=C1)S(=O)(=NC)C)N(C(=N2)O[C@@H]2CO[C@H]1[C@@H]2OC[C@H]1O)COCC[Si](C)(C)C VZPGBGXVBHZSQG-RSZYDNOISA-N 0.000 description 5
• 208000032928 Dyslipidaemia Diseases 0.000 description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 description 5
• 229910002666 PdCl2 Inorganic materials 0.000 description 5
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
• 208000017442 Retinal disease Diseases 0.000 description 5
• 206010038923 Retinopathy Diseases 0.000 description 5
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 125000005842 heteroatom Chemical group 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 201000001119 neuropathy Diseases 0.000 description 5
• 230000007823 neuropathy Effects 0.000 description 5
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• VFSHUOASIOCCAA-UHFFFAOYSA-N (4-bromophenyl)-imino-methyl-oxo-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1=CC=C(Br)C=C1 VFSHUOASIOCCAA-UHFFFAOYSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 4
• 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 4
• 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 4
• 108010018763 Biotin carboxylase Proteins 0.000 description 4
• BZKQBNCSEFBDEI-UHFFFAOYSA-N CS(=N)(=O)c1ccc(nc1)-c1ccc(Br)cc1 Chemical compound CS(=N)(=O)c1ccc(nc1)-c1ccc(Br)cc1 BZKQBNCSEFBDEI-UHFFFAOYSA-N 0.000 description 4
• 208000031226 Hyperlipidaemia Diseases 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• DORJPKIXOSSJQD-UHFFFAOYSA-N [(4-bromophenyl)-methyl-oxo-$l^{6}-sulfanylidene]cyanamide Chemical compound N#CN=S(=O)(C)C1=CC=C(Br)C=C1 DORJPKIXOSSJQD-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 238000000502 dialysis Methods 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 201000001421 hyperglycemia Diseases 0.000 description 4
• YFYIDTVGWCYSEO-UHFFFAOYSA-N imino-methyl-oxo-phenyl-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1=CC=CC=C1 YFYIDTVGWCYSEO-UHFFFAOYSA-N 0.000 description 4
• 208000017169 kidney disease Diseases 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 4
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 4
• 235000011181 potassium carbonates Nutrition 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 4
• CTIMVZSQYDXRAP-UHFFFAOYSA-N (3-bromophenyl)imino-dimethyl-oxo-$l^{6}-sulfane Chemical compound CS(C)(=O)=NC1=CC=CC(Br)=C1 CTIMVZSQYDXRAP-UHFFFAOYSA-N 0.000 description 3
• WBJZLUNZRMPGNW-DEPWHIHDSA-N (3R,3aR,6R,6aR)-6-[5-(6-bromopyridin-3-yl)-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(Br)nc1 WBJZLUNZRMPGNW-DEPWHIHDSA-N 0.000 description 3
• ZWXSEKSZMBLYMF-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[5-[4-(4-bromopyridin-2-yl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cc(Br)ccn1 ZWXSEKSZMBLYMF-UDCKCYQBSA-N 0.000 description 3
• LUTWVOQLKZBACF-SAZLYLDSSA-N (3R,3aR,6R,6aR)-6-[5-[4-(5-bromopyrazin-2-yl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cnc(Br)cn1 LUTWVOQLKZBACF-SAZLYLDSSA-N 0.000 description 3
• WVNYMSYPLTZIOW-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[5-[4-(5-bromopyridin-2-yl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(Br)cn1 WVNYMSYPLTZIOW-UDCKCYQBSA-N 0.000 description 3
• MZIPCDYSOSGACV-WMMXXEOUSA-N (3R,3aR,6R,6aR)-6-[5-[4-(5-bromopyrimidin-2-yl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ncc(Br)cn1 MZIPCDYSOSGACV-WMMXXEOUSA-N 0.000 description 3
• JOJNCBMEXWMBEK-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[5-[6-(4-bromophenyl)pyridin-3-yl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(nc1)-c1ccc(Br)cc1 JOJNCBMEXWMBEK-UDCKCYQBSA-N 0.000 description 3
• ZDWGBROVLULVMN-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[2-[4-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]pyrimidin-5-yl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1cnc(nc1)-c1ccc(cc1)N=S(C)(C)=O ZDWGBROVLULVMN-UDCKCYQBSA-N 0.000 description 3
• QTLOUTXUDFZTPJ-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2nc(c(Cl)cc12)-c1ccc(cc1)C1=CCSCC1 QTLOUTXUDFZTPJ-UDCKCYQBSA-N 0.000 description 3
• AQUCMGZLIABINI-VMZVKWDOSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(5-methylsulfinylpyrimidin-2-yl)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CS(=O)c1cnc(nc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl AQUCMGZLIABINI-VMZVKWDOSA-N 0.000 description 3
• HPEISSIAKPKKJE-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(thian-4-yl)phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2nc(c(Cl)cc12)-c1ccc(cc1)C1CCSCC1 HPEISSIAKPKKJE-UDCKCYQBSA-N 0.000 description 3
• UJLILPWKEZAVCX-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[2-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]pyridin-4-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccnc(CN=S(C)(C)=O)c1 UJLILPWKEZAVCX-XQQPTAJKSA-N 0.000 description 3
• KWFZHBVHEAHKCA-WPUBFDFZSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[2-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridin-4-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccnc(c1)N=S(C)(C)=O KWFZHBVHEAHKCA-WPUBFDFZSA-N 0.000 description 3
• GFKYKRJNRKSBEU-ZSLXANFHSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[3-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cccc(CN=S(C)(C)=O)c1 GFKYKRJNRKSBEU-ZSLXANFHSA-N 0.000 description 3
• REZVVENLCCKSEJ-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[3-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cccc(c1)N=S(C)(C)=O REZVVENLCCKSEJ-XQQPTAJKSA-N 0.000 description 3
• UCOAFTFYUVSALL-IQTJWYDPSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-(N,S-dimethylsulfonimidoyl)phenyl]piperazin-1-yl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound ClC=1C=C2C(=NC=1N1CCN(CC1)C1=CC=C(C=C1)S(=O)(=NC)C)N(C(=N2)O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2O)COCC[Si](C)(C)C UCOAFTFYUVSALL-IQTJWYDPSA-N 0.000 description 3
• JKYBYYPOPNQVIS-ZSLXANFHSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(CN=S(C)(C)=O)cc1 JKYBYYPOPNQVIS-ZSLXANFHSA-N 0.000 description 3
• BLQAJKIFPAWLPW-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]piperidin-1-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N1CCC(CN=S(C)(C)=O)CC1 BLQAJKIFPAWLPW-XQQPTAJKSA-N 0.000 description 3
• CGOFSOIVHJGLHU-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cc(CN=S(C)(C)=O)ccn1 CGOFSOIVHJGLHU-XQQPTAJKSA-N 0.000 description 3
• QGQQAPTXEAIBEZ-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cc1)N=S(C)(C)=O QGQQAPTXEAIBEZ-XQQPTAJKSA-N 0.000 description 3
• PABRHUFGTQGVPL-BOXYVWFNSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cc(ccn1)N=S(C)(C)=O PABRHUFGTQGVPL-BOXYVWFNSA-N 0.000 description 3
• UMFZBSYBTZMWQA-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(CN=S(C)(C)=O)cn1 UMFZBSYBTZMWQA-XQQPTAJKSA-N 0.000 description 3
• WFSJBGCLVSLBCB-DHPILJFKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-1,3-dihydroisoindol-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N1Cc2ccc(cc2C1)N=S(C)(C)=O WFSJBGCLVSLBCB-DHPILJFKSA-N 0.000 description 3
• QVASVFZOYZKJJP-NFFAYCCRSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyrazin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cnc(cn1)N=S(C)(C)=O QVASVFZOYZKJJP-NFFAYCCRSA-N 0.000 description 3
• HNBKDVKYHAYXNB-BOXYVWFNSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cn1)N=S(C)(C)=O HNBKDVKYHAYXNB-BOXYVWFNSA-N 0.000 description 3
• IUOAVDBTUZDWGN-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyrimidin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ncc(cn1)N=S(C)(C)=O IUOAVDBTUZDWGN-UDCKCYQBSA-N 0.000 description 3
• GZLIBLIKLZCHKV-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[6-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cccc(CN=S(C)(C)=O)n1 GZLIBLIKLZCHKV-XQQPTAJKSA-N 0.000 description 3
• YFLIPQMJKBSCKT-XQQPTAJKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[6-[[[dimethyl(oxo)-lambda6-sulfanylidene]amino]methyl]pyridin-3-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(CN=S(C)(C)=O)nc1 YFLIPQMJKBSCKT-XQQPTAJKSA-N 0.000 description 3
• LUUMINQLNGPIPH-NFFAYCCRSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridazin-3-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(N=S(C)(C)=O)nn1 LUUMINQLNGPIPH-NFFAYCCRSA-N 0.000 description 3
• GYWIHRLTKFJLMG-WPUBFDFZSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridin-2-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cccc(N=S(C)(C)=O)n1 GYWIHRLTKFJLMG-WPUBFDFZSA-N 0.000 description 3
• HQAKHTFYAKABJJ-WPUBFDFZSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]pyridin-3-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(N=S(C)(C)=O)nc1 HQAKHTFYAKABJJ-WPUBFDFZSA-N 0.000 description 3
• QTCVMPKVWAYZRI-LUGTWXOSSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N=S(C)(C)=O QTCVMPKVWAYZRI-LUGTWXOSSA-N 0.000 description 3
• CRVZMTWMPYNWBE-BOXYVWFNSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[6-[4-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]pyridin-3-yl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(nc1)-c1ccc(cc1)N=S(C)(C)=O CRVZMTWMPYNWBE-BOXYVWFNSA-N 0.000 description 3
• DSCCGCLXKGDOMB-NCXUSEDFSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-piperazin-1-yl-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)N1CCNCC1 DSCCGCLXKGDOMB-NCXUSEDFSA-N 0.000 description 3
• RTQSXUUJYSEFNG-UHFFFAOYSA-N (4-bromophenyl)-methyl-methylimino-oxo-$l^{6}-sulfane Chemical compound CN=S(C)(=O)C1=CC=C(Br)C=C1 RTQSXUUJYSEFNG-UHFFFAOYSA-N 0.000 description 3
• QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 3
• MLZHEHPWIFVXTG-UHFFFAOYSA-N 2-[(6-chloro-5-iodo-2-methylsulfonylimidazo[4,5-b]pyridin-3-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCn1c(nc2cc(Cl)c(I)nc12)S(C)(=O)=O MLZHEHPWIFVXTG-UHFFFAOYSA-N 0.000 description 3
• ZVUHIPJSZBEXED-UHFFFAOYSA-N 2-bromo-5-methylsulfinylpyridine Chemical compound CS(=O)C1=CC=C(Br)N=C1 ZVUHIPJSZBEXED-UHFFFAOYSA-N 0.000 description 3
• COSIOKPASQSOLN-LUGTWXOSSA-N 4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]-N-[dimethyl(oxo)-lambda6-sulfanylidene]benzamide Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)C(=O)N=S(C)(C)=O COSIOKPASQSOLN-LUGTWXOSSA-N 0.000 description 3
• DWOZNANUEDYIOF-UHFFFAOYSA-L 4-ditert-butylphosphanyl-n,n-dimethylaniline;dichloropalladium Chemical compound Cl[Pd]Cl.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 DWOZNANUEDYIOF-UHFFFAOYSA-L 0.000 description 3
• ONODTODRMPFABG-UHFFFAOYSA-N 5-benzyl-1,3,3a,4,6,6a-hexahydrothieno[3,4-c]pyrrole Chemical compound C1C2CSCC2CN1CC1=CC=CC=C1 ONODTODRMPFABG-UHFFFAOYSA-N 0.000 description 3
• JPFHBPIWPMDITA-UHFFFAOYSA-N BrC1=CC=C(C=C1)C1=NC=C(C=C1)S(=O)(=NC)C Chemical compound BrC1=CC=C(C=C1)C1=NC=C(C=C1)S(=O)(=NC)C JPFHBPIWPMDITA-UHFFFAOYSA-N 0.000 description 3
• AGAZSGHJLORODJ-JHWYVYTCSA-N C(C)(C)(C)[Si](O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2OC2=NC=1C(=NC(=C(C1)Cl)C1=CC=C(C=C1)[C@@H]1CC[C@H](CC1)O)N2COCC[Si](C)(C)C)(C)C Chemical compound C(C)(C)(C)[Si](O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2OC2=NC=1C(=NC(=C(C1)Cl)C1=CC=C(C=C1)[C@@H]1CC[C@H](CC1)O)N2COCC[Si](C)(C)C)(C)C AGAZSGHJLORODJ-JHWYVYTCSA-N 0.000 description 3
• DKAGVRVUWOKVPY-UHFFFAOYSA-N CC(C)(C)OC(=O)N=S(C)(=O)c1ccc(nc1)-c1ccc(Br)cc1 Chemical compound CC(C)(C)OC(=O)N=S(C)(=O)c1ccc(nc1)-c1ccc(Br)cc1 DKAGVRVUWOKVPY-UHFFFAOYSA-N 0.000 description 3
• IINBXPQKUHMEAM-UHFFFAOYSA-N CC(C)(C)OC(=O)NCC1CCN(CC1)c1ccc(Br)cc1 Chemical compound CC(C)(C)OC(=O)NCC1CCN(CC1)c1ccc(Br)cc1 IINBXPQKUHMEAM-UHFFFAOYSA-N 0.000 description 3
• ODWJAQMJCRYSGZ-KOMQPUFPSA-N CC1(C)OB(OC1(C)C)c1ccc(cc1)[C@H]1CC[C@H](O)CC1 Chemical compound CC1(C)OB(OC1(C)C)c1ccc(cc1)[C@H]1CC[C@H](O)CC1 ODWJAQMJCRYSGZ-KOMQPUFPSA-N 0.000 description 3
• HWKQBKYKNLLPFY-UHFFFAOYSA-N CS(=O)(=NC(=O)C(F)(F)F)c1cccc(Br)c1 Chemical compound CS(=O)(=NC(=O)C(F)(F)F)c1cccc(Br)c1 HWKQBKYKNLLPFY-UHFFFAOYSA-N 0.000 description 3
• QPKDIPKASMXTHJ-UHFFFAOYSA-N CS(=O)c1cnc(Cl)nc1 Chemical compound CS(=O)c1cnc(Cl)nc1 QPKDIPKASMXTHJ-UHFFFAOYSA-N 0.000 description 3
• VLYQDPORTXTESW-UHFFFAOYSA-N CS(C)(=O)=NCC1CCN(CC1)c1ccc(Br)cc1 Chemical compound CS(C)(=O)=NCC1CCN(CC1)c1ccc(Br)cc1 VLYQDPORTXTESW-UHFFFAOYSA-N 0.000 description 3
• LBBDDCQEEQWWSC-UHFFFAOYSA-N CS(C)(=O)=NCc1cc(Br)ccn1 Chemical compound CS(C)(=O)=NCc1cc(Br)ccn1 LBBDDCQEEQWWSC-UHFFFAOYSA-N 0.000 description 3
• VJYSVAJQPOYGSL-UHFFFAOYSA-N CS(C)(=O)=NCc1ccc(Br)cc1 Chemical compound CS(C)(=O)=NCc1ccc(Br)cc1 VJYSVAJQPOYGSL-UHFFFAOYSA-N 0.000 description 3
• ABDMYDXSLIGEMB-UHFFFAOYSA-N CS(C)(=O)=NCc1ccc(Br)cn1 Chemical compound CS(C)(=O)=NCc1ccc(Br)cn1 ABDMYDXSLIGEMB-UHFFFAOYSA-N 0.000 description 3
• RZYIKKCVCQDDMC-UHFFFAOYSA-N CS(C)(=O)=NCc1ccc(Br)nc1 Chemical compound CS(C)(=O)=NCc1ccc(Br)nc1 RZYIKKCVCQDDMC-UHFFFAOYSA-N 0.000 description 3
• ANLDTXIPVZROAY-UHFFFAOYSA-N CS(C)(=O)=NCc1cccc(Br)c1 Chemical compound CS(C)(=O)=NCc1cccc(Br)c1 ANLDTXIPVZROAY-UHFFFAOYSA-N 0.000 description 3
• TWOBELJAVSKAOD-UHFFFAOYSA-N CS(C)(=O)=NCc1ccnc(Br)c1 Chemical compound CS(C)(=O)=NCc1ccnc(Br)c1 TWOBELJAVSKAOD-UHFFFAOYSA-N 0.000 description 3
• MQKGSWJKDSDMEO-UHFFFAOYSA-N CS(C)(=O)=Nc1ccc(Br)cn1 Chemical compound CS(C)(=O)=Nc1ccc(Br)cn1 MQKGSWJKDSDMEO-UHFFFAOYSA-N 0.000 description 3
• PSHOPHFMHGXXMS-UHFFFAOYSA-N CS(C)(=O)=Nc1ccc(Br)nn1 Chemical compound CS(C)(=O)=Nc1ccc(Br)nn1 PSHOPHFMHGXXMS-UHFFFAOYSA-N 0.000 description 3
• ZFCZKMSJKHXUAV-UHFFFAOYSA-N CS(C)(=O)=Nc1ccc(cc1)-c1ncc(Br)cn1 Chemical compound CS(C)(=O)=Nc1ccc(cc1)-c1ncc(Br)cn1 ZFCZKMSJKHXUAV-UHFFFAOYSA-N 0.000 description 3
• FSNXQVPEWIWHSU-UHFFFAOYSA-N CS(C)(=O)=Nc1cccc(Br)n1 Chemical compound CS(C)(=O)=Nc1cccc(Br)n1 FSNXQVPEWIWHSU-UHFFFAOYSA-N 0.000 description 3
• MAABSPFAAGILBB-KBUPBQIOSA-N C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(Cl)nc12 Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(Cl)nc12 MAABSPFAAGILBB-KBUPBQIOSA-N 0.000 description 3
• ONFTVVCZRGDZMW-CDRKEARJSA-N C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cc1)C(O)=O Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cc1)C(O)=O ONFTVVCZRGDZMW-CDRKEARJSA-N 0.000 description 3
• RNXONYSIPFGORM-UDCKCYQBSA-N C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)C1=CCSCC1 Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)C1=CCSCC1 RNXONYSIPFGORM-UDCKCYQBSA-N 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• UNCNAPHPRTURHZ-UHFFFAOYSA-N Cl.CS(C)(=O)=Nc1ccc2CNCc2c1 Chemical compound Cl.CS(C)(=O)=Nc1ccc2CNCc2c1 UNCNAPHPRTURHZ-UHFFFAOYSA-N 0.000 description 3
• NKIXVPJGZDAZDE-UHFFFAOYSA-N Cl.CS(C)(=O)=Nc1ccc2CNCc2n1 Chemical compound Cl.CS(C)(=O)=Nc1ccc2CNCc2n1 NKIXVPJGZDAZDE-UHFFFAOYSA-N 0.000 description 3
• KUEIQRBNBVTISO-UHFFFAOYSA-N Clc1cc2[nH]c(=S)[nH]c2nc1Cl Chemical compound Clc1cc2[nH]c(=S)[nH]c2nc1Cl KUEIQRBNBVTISO-UHFFFAOYSA-N 0.000 description 3
• 229920002307 Dextran Polymers 0.000 description 3
• 208000008960 Diabetic foot Diseases 0.000 description 3
• 206010063547 Diabetic macroangiopathy Diseases 0.000 description 3
• 206010056340 Diabetic ulcer Diseases 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 102000016267 Leptin Human genes 0.000 description 3
• 108010092277 Leptin Proteins 0.000 description 3
• 208000017170 Lipid metabolism disease Diseases 0.000 description 3
• CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• SCJNWGSYQHIEFU-ZFVBIPRHSA-N N-[[2-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]pyrimidin-5-yl]-methyl-oxo-lambda6-sulfanylidene]-2,2,2-trifluoroacetamide Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ncc(cn1)S(C)(=O)=NC(=O)C(F)(F)F SCJNWGSYQHIEFU-ZFVBIPRHSA-N 0.000 description 3
• CDCZTQQFEIILBI-ARAFUBJGSA-N N-[[3-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]-methyl-oxo-lambda6-sulfanylidene]-2,2,2-trifluoroacetamide Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1cccc(c1)S(C)(=O)=NC(=O)C(F)(F)F CDCZTQQFEIILBI-ARAFUBJGSA-N 0.000 description 3
• SHDMTJJTRULXBO-UHFFFAOYSA-N O=C(OCc1ccccc1)N1CC2CSCC2C1 Chemical compound O=C(OCc1ccccc1)N1CC2CSCC2C1 SHDMTJJTRULXBO-UHFFFAOYSA-N 0.000 description 3
• 206010033307 Overweight Diseases 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• FFWNNHIBBBWEQN-UHFFFAOYSA-N [(4-bromophenyl)-methyl-$l^{4}-sulfanylidene]cyanamide Chemical compound N#CN=S(C)C1=CC=C(Br)C=C1 FFWNNHIBBBWEQN-UHFFFAOYSA-N 0.000 description 3
• RXKICBLQDKHVIG-UHFFFAOYSA-N [1-(4-bromophenyl)piperidin-4-yl]methanamine Chemical compound C1CC(CN)CCN1C1=CC=C(Br)C=C1 RXKICBLQDKHVIG-UHFFFAOYSA-N 0.000 description 3
• DCIJWSVKVWQFQS-QZZBVQKOSA-N [[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]-methyl-oxo-lambda6-sulfanylidene]cyanamide Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cc1)S(C)(=O)=NC#N DCIJWSVKVWQFQS-QZZBVQKOSA-N 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 239000003472 antidiabetic agent Substances 0.000 description 3
• 125000000732 arylene group Chemical group 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
• ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 3
• PPCSEQIXCANFRZ-UHFFFAOYSA-N dimethyl-oxo-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]imino-lambda6-sulfane Chemical compound CC1(C)OB(OC1(C)C)c1ccc(cc1)N=S(C)(C)=O PPCSEQIXCANFRZ-UHFFFAOYSA-N 0.000 description 3
• HJBCNNCSLXEKQN-UHFFFAOYSA-N dimethyl-oxo-[[1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidin-4-yl]methylimino]-lambda6-sulfane Chemical compound CC1(C)OB(OC1(C)C)c1ccc(cc1)N1CCC(CN=S(C)(C)=O)CC1 HJBCNNCSLXEKQN-UHFFFAOYSA-N 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical group OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
• 125000005549 heteroarylene group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 210000004153 islets of langerhan Anatomy 0.000 description 3
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 3
• 229940039781 leptin Drugs 0.000 description 3
• 238000004020 luminiscence type Methods 0.000 description 3
• WNZKOCAFRFLVNV-UHFFFAOYSA-N methyl-methylimino-oxo-[6-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyridin-3-yl]-lambda6-sulfane Chemical compound CN=S(=O)(C)C=1C=CC(=NC1)C1=CC=C(C=C1)B1OC(C(O1)(C)C)(C)C WNZKOCAFRFLVNV-UHFFFAOYSA-N 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 125000005576 pyrimidinylene group Chemical group 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 210000002027 skeletal muscle Anatomy 0.000 description 3
• 239000011550 stock solution Substances 0.000 description 3
• 150000003462 sulfoxides Chemical class 0.000 description 3
• 235000011149 sulphuric acid Nutrition 0.000 description 3
• LUFMRTVBWALXAA-ZNEDAJEESA-N tert-butyl N-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]-methyl-oxo-lambda6-sulfanylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=S(C)(=O)c1ccc(cc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl LUFMRTVBWALXAA-ZNEDAJEESA-N 0.000 description 3
• NQEZXWYHMPAWBP-INEXWBNUSA-N tert-butyl N-[[6-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]pyridin-3-yl]-methyl-oxo-lambda6-sulfanylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=S(C)(=O)c1ccc(nc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl NQEZXWYHMPAWBP-INEXWBNUSA-N 0.000 description 3
• KYKDTQHVNGEOPM-UHFFFAOYSA-N tert-butyl N-[methyl-oxo-[6-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyridin-3-yl]-lambda6-sulfanylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=S(C)(=O)c1ccc(nc1)-c1ccc(cc1)B1OC(C)(C)C(C)(C)O1 KYKDTQHVNGEOPM-UHFFFAOYSA-N 0.000 description 3
• UOROYTLLUGSWMG-UHFFFAOYSA-N tert-butyl n-[(4-bromophenyl)-methyl-oxo-$l^{6}-sulfanylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=S(C)(=O)C1=CC=C(Br)C=C1 UOROYTLLUGSWMG-UHFFFAOYSA-N 0.000 description 3
• 231100000397 ulcer Toxicity 0.000 description 3
• 239000013598 vector Substances 0.000 description 3
• 229910052727 yttrium Inorganic materials 0.000 description 3
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
• YWHYQLDWVIWIOS-FKDDUOCFSA-N (3R,3aR,6R,6aR)-6-[5-[4-(2-bromopyridin-4-yl)phenyl]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccnc(Br)c1 YWHYQLDWVIWIOS-FKDDUOCFSA-N 0.000 description 2
• FIRAKWSYVIGLLJ-GERHYJQASA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[2-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5,7-dihydropyrrolo[3,4-b]pyridin-6-yl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N1Cc2ccc(N=S(C)(C)=O)nc2C1 FIRAKWSYVIGLLJ-GERHYJQASA-N 0.000 description 2
• RODPUXVNYAIXKS-UGESXGAOSA-N (3r,3ar,6r,6ar)-6-[5-(4-bromophenyl)-6-chloro-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound ClC=1C=C2N(COCC[Si](C)(C)C)C(O[C@H]3[C@H]4OC[C@@H](O)[C@H]4OC3)=NC2=NC=1C1=CC=C(Br)C=C1 RODPUXVNYAIXKS-UGESXGAOSA-N 0.000 description 2
• BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical class CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 2
• ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 2
• QZVRTORVCKGPPY-UHFFFAOYSA-N 2-(3,6-dihydro-2h-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CCSCC1 QZVRTORVCKGPPY-UHFFFAOYSA-N 0.000 description 2
• UBDWUSXGYNLMFY-UHFFFAOYSA-N 2-[(5,6-dichloro-2-methylsulfonylimidazo[4,5-b]pyridin-3-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCn1c(nc2cc(Cl)c(Cl)nc12)S(C)(=O)=O UBDWUSXGYNLMFY-UHFFFAOYSA-N 0.000 description 2
• GSVQWRYRPRJOIM-UHFFFAOYSA-N 2-methylpropan-2-ol;sodium Chemical compound [Na].CC(C)(C)O GSVQWRYRPRJOIM-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• NDXVNFXIIDXXNL-UHFFFAOYSA-N 4-(5-ethylfuran-2-yl)-2-methoxyphenol Chemical compound O1C(CC)=CC=C1C1=CC=C(O)C(OC)=C1 NDXVNFXIIDXXNL-UHFFFAOYSA-N 0.000 description 2
• SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 2
• ZEZKXPQIDURFKA-UHFFFAOYSA-N 5-bromo-2-iodopyrimidine Chemical compound BrC1=CN=C(I)N=C1 ZEZKXPQIDURFKA-UHFFFAOYSA-N 0.000 description 2
• 108010017384 Blood Proteins Proteins 0.000 description 2
• 102000004506 Blood Proteins Human genes 0.000 description 2
• AMJAFDWYJANRKL-UHFFFAOYSA-N CS(=O)(=O)c1nc2nc(Cl)c(Cl)cc2[nH]1 Chemical compound CS(=O)(=O)c1nc2nc(Cl)c(Cl)cc2[nH]1 AMJAFDWYJANRKL-UHFFFAOYSA-N 0.000 description 2
• GVAMUSQAHIWACM-UHFFFAOYSA-N CS(C)(=O)=NCc1cccc(Br)n1 Chemical compound CS(C)(=O)=NCc1cccc(Br)n1 GVAMUSQAHIWACM-UHFFFAOYSA-N 0.000 description 2
• FCCQWNHUMAKDSH-UHFFFAOYSA-N CSC1Nc2cc(Cl)c(Cl)nc2N1 Chemical compound CSC1Nc2cc(Cl)c(Cl)nc2N1 FCCQWNHUMAKDSH-UHFFFAOYSA-N 0.000 description 2
• 206010007558 Cardiac failure chronic Diseases 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 2
• 101710091951 Glycerol-3-phosphate acyltransferase Proteins 0.000 description 2
• 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 2
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 2
• 241000192132 Leuconostoc Species 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 229910007161 Si(CH3)3 Inorganic materials 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 238000006069 Suzuki reaction reaction Methods 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 229940125708 antidiabetic agent Drugs 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 239000003613 bile acid Substances 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 235000010290 biphenyl Nutrition 0.000 description 2
• 238000004364 calculation method Methods 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 2
• 239000002934 diuretic Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 230000004190 glucose uptake Effects 0.000 description 2
• 229960003180 glutathione Drugs 0.000 description 2
• 235000003969 glutathione Nutrition 0.000 description 2
• 230000002641 glycemic effect Effects 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• 230000035879 hyperinsulinaemia Effects 0.000 description 2
• 150000005232 imidazopyridines Chemical class 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000003914 insulin secretion Effects 0.000 description 2
• 208000001921 latent autoimmune diabetes in adults Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 239000000395 magnesium oxide Substances 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• OTYPIDNRISCWQY-UHFFFAOYSA-L palladium(2+);tris(2-methylphenyl)phosphane;dichloride Chemical compound Cl[Pd]Cl.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C OTYPIDNRISCWQY-UHFFFAOYSA-L 0.000 description 2
• 208000033808 peripheral neuropathy Diseases 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000010948 rhodium Substances 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
• 150000003568 thioethers Chemical class 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 241000701447 unidentified baculovirus Species 0.000 description 2
• UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
• YPKKUAWNZPRPQW-UDCKCYQBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(1-methylimino-1-oxo-1,4-thiazinan-4-yl)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CN=S1(=O)CCN(CC1)c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl YPKKUAWNZPRPQW-UDCKCYQBSA-N 0.000 description 1
• UJNSWGJWROMKHM-AHBCNTCXSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[(methyl-oxo-phenyl-lambda6-sulfanylidene)amino]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N=[S@@](C)(=O)c1ccccc1 UJNSWGJWROMKHM-AHBCNTCXSA-N 0.000 description 1
• UJNSWGJWROMKHM-UXCHCDQYSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[(methyl-oxo-phenyl-lambda6-sulfanylidene)amino]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N=[S@](C)(=O)c1ccccc1 UJNSWGJWROMKHM-UXCHCDQYSA-N 0.000 description 1
• PBIURQAJBIUYFP-MPRKYAFTSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[(methyl-oxo-pyridin-4-yl-lambda6-sulfanylidene)amino]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)N=S(C)(=O)c1ccncc1 PBIURQAJBIUYFP-MPRKYAFTSA-N 0.000 description 1
• CKAZHNIHNMIYMU-RSACHPBBSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-(N,S-dimethylsulfonimidoyl)phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound ClC=1C=C2C(=NC=1C1=CC=C(C=C1)C1=CC=C(C=C1)S(=O)(=NC)C)N(C(=N2)O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2O)COCC[Si](C)(C)C CKAZHNIHNMIYMU-RSACHPBBSA-N 0.000 description 1
• ZVZLGBBFHSVPQF-XJMGTDGNSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[(cyclopropyl-methyl-oxo-lambda6-sulfanylidene)amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C[Si](C)(C)CCOCn1c(O[C@@H]2CO[C@@H]3[C@H](O)CO[C@H]23)nc2cc(Cl)c(nc12)-c1ccc(cc1)-c1ccc(cc1)N=S(C)(=O)C1CC1 ZVZLGBBFHSVPQF-XJMGTDGNSA-N 0.000 description 1
• NRWHIFUYBSSIET-OHLWHAAESA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[(ethyl-methyl-oxo-lambda6-sulfanylidene)amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CCS(C)(=O)=Nc1ccc(cc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl NRWHIFUYBSSIET-OHLWHAAESA-N 0.000 description 1
• AKBMCCRTDJCEIW-XJMGTDGNSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[(methyl-oxo-propan-2-yl-lambda6-sulfanylidene)amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CC(C)S(C)(=O)=Nc1ccc(cc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl AKBMCCRTDJCEIW-XJMGTDGNSA-N 0.000 description 1
• ATWZVINIJJJQRD-DHPILJFKSA-N (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[4-[[diethyl(oxo)-lambda6-sulfanylidene]amino]phenyl]phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound CCS(=O)(CC)=Nc1ccc(cc1)-c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl ATWZVINIJJJQRD-DHPILJFKSA-N 0.000 description 1
• KLDXJTOLSGUMSJ-KVTDHHQDSA-N (3r,3ar,6r,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-KVTDHHQDSA-N 0.000 description 1
• IRADHOWSAHPJAJ-UHFFFAOYSA-N (4-bromophenyl)imino-dimethyl-oxo-$l^{6}-sulfane Chemical compound CS(C)(=O)=NC1=CC=C(Br)C=C1 IRADHOWSAHPJAJ-UHFFFAOYSA-N 0.000 description 1
• BCYWDUVHAPHGIP-UHFFFAOYSA-N (6-bromopyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(Br)N=C1 BCYWDUVHAPHGIP-UHFFFAOYSA-N 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
• ZPCJPJQUVRIILS-UHFFFAOYSA-N 1-bromo-3-(bromomethyl)benzene Chemical compound BrCC1=CC=CC(Br)=C1 ZPCJPJQUVRIILS-UHFFFAOYSA-N 0.000 description 1
• CTPUUDQIXKUAMO-UHFFFAOYSA-N 1-bromo-3-iodobenzene Chemical compound BrC1=CC=CC(I)=C1 CTPUUDQIXKUAMO-UHFFFAOYSA-N 0.000 description 1
• FAGYVSVOUYMGTM-UHFFFAOYSA-N 1-bromo-3-methylsulfinylbenzene Chemical compound CS(=O)C1=CC=CC(Br)=C1 FAGYVSVOUYMGTM-UHFFFAOYSA-N 0.000 description 1
• YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
• ZCKYGWLZZOZAEP-UHFFFAOYSA-N 1-bromo-4-(methylsulfinylmethyl)benzene Chemical compound CS(=O)CC1=CC=C(Br)C=C1 ZCKYGWLZZOZAEP-UHFFFAOYSA-N 0.000 description 1
• UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 1
• YEUYZNNBXLMFCW-UHFFFAOYSA-N 1-bromo-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(Br)C=C1 YEUYZNNBXLMFCW-UHFFFAOYSA-N 0.000 description 1
• UIBWDNFGDBQBDK-UHFFFAOYSA-N 1-iminothiane 1-oxide Chemical compound N=S1(=O)CCCCC1 UIBWDNFGDBQBDK-UHFFFAOYSA-N 0.000 description 1
• NMBDLXYCYHEBDJ-UHFFFAOYSA-N 1-iminothiolane 1-oxide Chemical compound N=S1(=O)CCCC1 NMBDLXYCYHEBDJ-UHFFFAOYSA-N 0.000 description 1
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
• PCMMSLVJMKQWMQ-UHFFFAOYSA-N 2,4-dibromopyridine Chemical compound BrC1=CC=NC(Br)=C1 PCMMSLVJMKQWMQ-UHFFFAOYSA-N 0.000 description 1
• KIYKHEOWZLJZSB-UHFFFAOYSA-N 2,5-dibromopyrazine Chemical compound BrC1=CN=C(Br)C=N1 KIYKHEOWZLJZSB-UHFFFAOYSA-N 0.000 description 1
• JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
• FEYDZHNIIMENOB-UHFFFAOYSA-N 2,6-dibromopyridine Chemical compound BrC1=CC=CC(Br)=N1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 description 1
• BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• MWSJMNJBKAPIOX-UHFFFAOYSA-N 2-bromo-4-(bromomethyl)pyridine Chemical compound BrCC1=CC=NC(Br)=C1 MWSJMNJBKAPIOX-UHFFFAOYSA-N 0.000 description 1
• CRRMIKBAPPOPNW-UHFFFAOYSA-N 2-bromo-5-(bromomethyl)pyridine Chemical compound BrCC1=CC=C(Br)N=C1 CRRMIKBAPPOPNW-UHFFFAOYSA-N 0.000 description 1
• IFMCOWPTUPYFCT-UHFFFAOYSA-N 2-bromo-5-methylsulfanylpyridine Chemical compound CSC1=CC=C(Br)N=C1 IFMCOWPTUPYFCT-UHFFFAOYSA-N 0.000 description 1
• LSRDTCMNGSMEEI-UHFFFAOYSA-N 2-bromo-6-(bromomethyl)pyridine Chemical compound BrCC1=CC=CC(Br)=N1 LSRDTCMNGSMEEI-UHFFFAOYSA-N 0.000 description 1
• UGWJTFHCCZHCDI-UHFFFAOYSA-N 2-chloro-5-methylsulfanylpyrimidine Chemical compound CSC1=CN=C(Cl)N=C1 UGWJTFHCCZHCDI-UHFFFAOYSA-N 0.000 description 1
• VQAFMTSSCUETHA-UHFFFAOYSA-N 3,6-dibromopyridazine Chemical compound BrC1=CC=C(Br)N=N1 VQAFMTSSCUETHA-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• ADHJWVUGJNQQDD-UHFFFAOYSA-N 4-bromo-2-(bromomethyl)pyridine Chemical compound BrCC1=CC(Br)=CC=N1 ADHJWVUGJNQQDD-UHFFFAOYSA-N 0.000 description 1
• UGKYIHYYWHSBPK-UHFFFAOYSA-N 4-imino-1,4-oxathiane 4-oxide Chemical compound N=S1(=O)CCOCC1 UGKYIHYYWHSBPK-UHFFFAOYSA-N 0.000 description 1
• 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
• 102100038074 5'-AMP-activated protein kinase subunit beta-1 Human genes 0.000 description 1
• CHGCWQGIACIHHI-UHFFFAOYSA-N 5,6-dichloropyridine-2,3-diamine Chemical compound NC1=CC(Cl)=C(Cl)N=C1N CHGCWQGIACIHHI-UHFFFAOYSA-N 0.000 description 1
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
• IPEMCIBPDYCJLO-UHFFFAOYSA-N 5-[(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)methyl]-n-(2,4,6-trimethoxyphenyl)furan-2-carboxamide Chemical compound COC1=CC(OC)=CC(OC)=C1NC(=O)C(O1)=CC=C1CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C IPEMCIBPDYCJLO-UHFFFAOYSA-N 0.000 description 1
• PKCHRWPMNDRVMI-UHFFFAOYSA-N 5-bromo-2-(bromomethyl)pyridine Chemical compound BrCC1=CC=C(Br)C=N1 PKCHRWPMNDRVMI-UHFFFAOYSA-N 0.000 description 1
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• CGPYBQNRXLDREJ-UHFFFAOYSA-N 6-chloro-5-iodo-2-methylsulfonyl-1h-imidazo[4,5-b]pyridine Chemical compound IC1=C(Cl)C=C2NC(S(=O)(=O)C)=NC2=N1 CGPYBQNRXLDREJ-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 238000003727 ADP Glo Kinase Assay Methods 0.000 description 1
• 208000010444 Acidosis Diseases 0.000 description 1
• 102000011690 Adiponectin Human genes 0.000 description 1
• 108010076365 Adiponectin Proteins 0.000 description 1
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 101100460776 Arabidopsis thaliana NPY2 gene Proteins 0.000 description 1
• 101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• GJDUJNLJJHRHJN-UAFMIMERSA-N CC(C)(C)[Si](C)(C)O[C@@H]1CO[C@@H]2[C@@H](CO[C@H]12)Oc1nc2cc(Cl)c(I)nc2n1COCC[Si](C)(C)C Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1CO[C@@H]2[C@@H](CO[C@H]12)Oc1nc2cc(Cl)c(I)nc2n1COCC[Si](C)(C)C GJDUJNLJJHRHJN-UAFMIMERSA-N 0.000 description 1
• GKQVUFLHQQMKPE-UHFFFAOYSA-N CS(=O)(=NC(=O)C(F)(F)F)c1ccc(nc1)-c1ccc(Br)cc1 Chemical compound CS(=O)(=NC(=O)C(F)(F)F)c1ccc(nc1)-c1ccc(Br)cc1 GKQVUFLHQQMKPE-UHFFFAOYSA-N 0.000 description 1
• IRVUYWCWTDIYFM-UHFFFAOYSA-N CS(=O)c1ccc(nc1)-c1ccc(Br)cc1 Chemical compound CS(=O)c1ccc(nc1)-c1ccc(Br)cc1 IRVUYWCWTDIYFM-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
• 208000003322 Coinfection Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• 206010014935 Enzyme abnormality Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
• 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
• 108091007911 GSKs Proteins 0.000 description 1
• 229940122904 Glucagon receptor antagonist Drugs 0.000 description 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 1
• 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
• 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
• 102100030488 HEAT repeat-containing protein 6 Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000742701 Homo sapiens 5'-AMP-activated protein kinase subunit beta-1 Proteins 0.000 description 1
• 101000990566 Homo sapiens HEAT repeat-containing protein 6 Proteins 0.000 description 1
• 101000801684 Homo sapiens Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 1
• 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 201000001431 Hyperuricemia Diseases 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000007976 Ketosis Diseases 0.000 description 1
• 108010081805 Malonyl-CoA decarboxylase Proteins 0.000 description 1
• 102100029461 Malonyl-CoA decarboxylase, mitochondrial Human genes 0.000 description 1
• 206010027417 Metabolic acidosis Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• DDZPETMBVJSOIC-CDRKEARJSA-N N-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]-1-oxo-1,4-thiazinan-1-ylidene]acetamide Chemical compound CC(=O)N=S1(=O)CCN(CC1)c1ccc(cc1)-c1nc2n(COCC[Si](C)(C)C)c(O[C@@H]3CO[C@@H]4[C@H](O)CO[C@H]34)nc2cc1Cl DDZPETMBVJSOIC-CDRKEARJSA-N 0.000 description 1
• 101150111774 NPY5R gene Proteins 0.000 description 1
• 102000003729 Neprilysin Human genes 0.000 description 1
• 108090000028 Neprilysin Proteins 0.000 description 1
• XFBZYNAECHJIDN-UHFFFAOYSA-N OC(=O)C(F)(F)F.CC(=O)N=S1(=O)CCNCC1 Chemical compound OC(=O)C(F)(F)F.CC(=O)N=S1(=O)CCNCC1 XFBZYNAECHJIDN-UHFFFAOYSA-N 0.000 description 1
• RPEGQKKCSVAXRU-UHFFFAOYSA-N OC(=O)C(F)(F)F.CN=S1(=O)CCNCC1 Chemical compound OC(=O)C(F)(F)F.CN=S1(=O)CCNCC1 RPEGQKKCSVAXRU-UHFFFAOYSA-N 0.000 description 1
• VGYAAWYHVAAJNX-UMSPYCQHSA-N O[C@H]1CC[C@@H](CC1)c1ccc(Br)cc1 Chemical compound O[C@H]1CC[C@@H](CC1)c1ccc(Br)cc1 VGYAAWYHVAAJNX-UMSPYCQHSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 102100040918 Pro-glucagon Human genes 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 108091006300 SLC2A4 Proteins 0.000 description 1
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
• 102000000019 Sterol Esterase Human genes 0.000 description 1
• 108010055297 Sterol Esterase Proteins 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 239000004809 Teflon Substances 0.000 description 1
• 229920006362 Teflon® Polymers 0.000 description 1
• 229940123464 Thiazolidinedione Drugs 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical class [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
• 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
• 101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 description 1
• QLMHBBHJAIQYGG-UHFFFAOYSA-N [1-benzyl-4-(methylsulfonyloxymethyl)pyrrolidin-3-yl]methyl methanesulfonate Chemical compound C1C(COS(C)(=O)=O)C(COS(=O)(=O)C)CN1CC1=CC=CC=C1 QLMHBBHJAIQYGG-UHFFFAOYSA-N 0.000 description 1
• HQAGDFJHKPSZHT-UHFFFAOYSA-N [4-(4-bromophenyl)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=C(Br)C=C1 HQAGDFJHKPSZHT-UHFFFAOYSA-N 0.000 description 1
• RLBSWXURKBYDRH-UHFFFAOYSA-N [N].C1=CC=C2NC=NC2=N1 Chemical compound [N].C1=CC=C2NC=NC2=N1 RLBSWXURKBYDRH-UHFFFAOYSA-N 0.000 description 1
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000001270 agonistic effect Effects 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
• 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
• 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 229940127003 anti-diabetic drug Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000003524 antilipemic agent Substances 0.000 description 1
• 239000003705 antithrombocytic agent Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000006470 autoimmune attack Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• NOJMTMIRQRDZMT-GSPXQYRGSA-N bromocriptine methanesulfonate Chemical compound CS(O)(=O)=O.C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 NOJMTMIRQRDZMT-GSPXQYRGSA-N 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000001364 causal effect Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• LNTPJYRBBKGUMA-UHFFFAOYSA-N cyclopropyl-imino-methyl-oxo-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1CC1 LNTPJYRBBKGUMA-UHFFFAOYSA-N 0.000 description 1
• 229940015838 cycloset Drugs 0.000 description 1
• 230000002498 deadly effect Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 230000002074 deregulated effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 239000000385 dialysis solution Substances 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• APAXYIMCLKHPKO-UHFFFAOYSA-N diethyl-imino-oxo-$l^{6}-sulfane Chemical compound CCS(=N)(=O)CC APAXYIMCLKHPKO-UHFFFAOYSA-N 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 208000016097 disease of metabolism Diseases 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 230000001882 diuretic effect Effects 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
• VGQYFOJSWJEAII-UHFFFAOYSA-N ethyl-imino-methyl-oxo-$l^{6}-sulfane Chemical compound CCS(C)(=N)=O VGQYFOJSWJEAII-UHFFFAOYSA-N 0.000 description 1
• 230000004129 fatty acid metabolism Effects 0.000 description 1
• 230000004136 fatty acid synthesis Effects 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 208000018914 glucose metabolism disease Diseases 0.000 description 1
• 230000006377 glucose transport Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002366 halogen compounds Chemical class 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 229960002003 hydrochlorothiazide Drugs 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• MDKMTCWSBSWOAS-UHFFFAOYSA-N imino-methyl-(oxan-4-yl)-oxo-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1CCOCC1 MDKMTCWSBSWOAS-UHFFFAOYSA-N 0.000 description 1
• WQTVBSJHCGLRDL-UHFFFAOYSA-N imino-methyl-oxo-propan-2-yl-$l^{6}-sulfane Chemical compound CC(C)S(C)(=N)=O WQTVBSJHCGLRDL-UHFFFAOYSA-N 0.000 description 1
• YVPALPQTUALGPB-UHFFFAOYSA-N imino-methyl-oxo-pyridin-3-yl-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1=CC=CN=C1 YVPALPQTUALGPB-UHFFFAOYSA-N 0.000 description 1
• ZPCGCFGKAOWNSE-UHFFFAOYSA-N imino-methyl-oxo-pyridin-4-yl-$l^{6}-sulfane Chemical compound CS(=N)(=O)C1=CC=NC=C1 ZPCGCFGKAOWNSE-UHFFFAOYSA-N 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 230000004140 ketosis Effects 0.000 description 1
• 230000004132 lipogenesis Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000006371 metabolic abnormality Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
• 229960003105 metformin Drugs 0.000 description 1
• XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
• DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 230000008113 positive regulation of fatty acid oxidation Effects 0.000 description 1
• 230000000291 postprandial effect Effects 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
• 229910000105 potassium hydride Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229910052703 rhodium Inorganic materials 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229910052979 sodium sulfide Inorganic materials 0.000 description 1
• GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000002636 symptomatic treatment Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• NAUMXRQXZPXPIW-UHFFFAOYSA-N tert-butyl 2-chloro-5,7-dihydropyrrolo[3,4-b]pyridine-6-carboxylate Chemical compound C1=C(Cl)N=C2CN(C(=O)OC(C)(C)C)CC2=C1 NAUMXRQXZPXPIW-UHFFFAOYSA-N 0.000 description 1
• GOKHEUCWNVPUSC-UHFFFAOYSA-N tert-butyl 5-bromo-1,3-dihydroisoindole-2-carboxylate Chemical compound C1=C(Br)C=C2CN(C(=O)OC(C)(C)C)CC2=C1 GOKHEUCWNVPUSC-UHFFFAOYSA-N 0.000 description 1
• VHYXAWLOJGIJPC-UHFFFAOYSA-N tert-butyl n-(piperidin-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNCC1 VHYXAWLOJGIJPC-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 230000010296 whole body energy metabolism Effects 0.000 description 1